Abstract 077: Protein Biomarkers Of Hypertension

Abstract

Background: Hypertension is a major modifiable riskfactor for cardiovascular disease. The discovery of novel protein biomarkers ofhypertension can provide information on disease pathophysiology and highlightpromising therapeutic targets. Methods: We measured plasma levels of 2925proteins in 740 participants (mean age 51.7 ±11.3 years; 46% women) in the Framingham HeartStudy using the Olink Explore proximity extension assay. Linear mixed modelswere used to explore the associations of plasma proteins with systolic anddiastolic blood pressure (BP) and prevalent hypertension. We definedhypertension as having elevated BP (systolic ≥ 140 mmHg or diastolic ≥90 mmHg) or current use of antihypertensive medication. We adjusted all themodels for age, sex, batch effects, eGFR (estimated glomerular filtration rate),pack-years of smoking, and lung function status (normal/obstructive/restrictive). Sensitivity analysis was performed by excluding individuals treated withantihypertensive medication. Using overrepresentation analysis, we annotatedthe proteins associated with hypertension. We adjusted for multiple tests using the Benjamini-Hochberg method and a false discovery rate of < 0.05 wasused to define statistical significance. Results: We observed differential expression of 526proteins (465 upregulated, 61 downregulated) in participants with prevalenthypertension (N=257) vs. normal BP (N= 483). Systolic BP was associated with571 proteins and diastolic BP was associated with 662 proteins. We observed 507protein associations with systolic BP and 626 protein associations withdiastolic BP after exclusion of treated individuals (N=177). Functionalannotation of proteins associated with hypertension showed enrichment of genesassociated with fatty acid transport, regulation of MAPK cascade, response tointerleukin-1 and inflammatory response. Discussion: This study elucidates protein signaturesassociated with BP and hypertension. Hypertension is enriched in pathwaysrelated to fatty acid transport and inflammatory response. These results mayprovide information on the pathogenesis ofhypertension and highlight promising therapeutic targets.